Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CHIP28 is an integral membrane protein that has been identified as the erythrocyte water channel and that is also expressed in the kidney. Antibodies against erythrocyte CHIP28 were used to localize this protein along the rat urinary tubule. By Western blotting, CHIP28 was detected in kidney plasma membrane and endosome fractions. With the use of immunocytochemistry, CHIP28 was located in brush-border and basolateral plasma membranes of the proximal tubule. The initial S1 segment was weakly stained, but the S2 and S3 segments were heavily labeled. Subapical vesicles were also positive. Apical and basolateral membranes of the long thin descending limb were strongly labeled, but ascending thin and thick limbs of Henle and distal convoluted tubules were negative. Some vasa recta profiles in the medulla were positive. CHIP28 is, therefore, present in membranes with a high constitutive water permeability, where it probably acts as a transmembrane water-conducting channel. Finally, a weak staining of apical and basolateral membranes of cortical collecting duct principal cells was detectable, suggesting a potential relationship of CHIP28 to the vasopressin-sensitive water channel.
 ...
PMID:Localization of the CHIP28 water channel in rat kidney. 128 99

The water channel CHIP28 accounts for the high water permeability of proximal tubules and thin descending limbs of Henle; a homologous water channel, WCH-CD, in the apical membrane of collecting duct principal cells, may be the vasopressin-sensitive water channel. We show here that one antiserum, raised against CHIP28, immunostains the basolateral membrane of collecting duct principal cells, in addition to staining CHIP28 in other cells. This serum was named anti-basolateral integral protein (anti-BLIP) to distinguish it from other anti-CHIP28 antisera. By Western blotting, BLIP serum recognized both CHIP28 and MIP26, and it stained lens fibers, which contain MIP26 but not CHIP28. BLIP antiserum immunoprecipitated a 28-kDa band, a broad 35- to 50-kDa band, and an approximately 16-kDa band from kidney papilla. It also stained the basolateral membrane of gastric parietal cells, which were not stained with anti-CHIP28 or anti-MIP26 antibodies. BLIP antiserum immunoprecipitated a 28-kDa protein band from stomach; this protein was not precipitated by anti-CHIP28 antibodies. These results suggest that basolateral membranes of principal cells and parietal cells contain a protein(s) that shares common epitopes with CHIP28 and MIP26. Finally, BLIP but not CHIP28 antiserum stained mesothelial (but not epithelial) cells of toad urinary bladder, a further indication that the BLIP antiserum recognizes a protein distinct from CHIP28.
 ...
PMID:A basolateral CHIP28/MIP26-related protein (BLIP) in kidney principal cells and gastric parietal cells. 752 36

Aquaporin 2 is a collecting duct water channel that is located in apical vesicles and in the apical plasma membrane of collecting duct principal cells. It shares 42% identity with the proximal tubule/thin descending limb water channel, CHIP28. The present study was aimed at addressing three questions concerning the location and behavior of the AQP2 protein under different conditions. First, does the AQP2 channel relocate to the apical membrane after vasopressin treatment? Our results show that AQP2 is diffusely distributed in cytoplasmic vesicles in collecting duct principal cells of homozygous Brattleboro rats that lack vasopressin. In rats injected with exogenous vasopressin, however, AQP2 became concentrated in the apical plasma membrane of principal cells, as determined by immunofluorescence and immunogold electron microscopy. This behavior is consistent with the idea that AQP2 is the vasopressin-sensitive water channel. Second, is the cellular location of AQP2 modified by microtubule disruption? In normal rats, AQP2 has a mainly apical and subapical location in principal cells, but in colchicine-treated rats, it is distributed on vesicles that are scattered throughout the entire cytoplasm. This is consistent with the dependence on microtubules of apical protein targeting in many cell types, and explains the inhibitory effect of microtubule disruption on the hydroosmotic response to vasopressin in sensitive epithelia, including the collecting duct. Third, is AQP2 present in neonatal rat kidneys? We show that AQP2 is abundant in principal cells from neonatal rats at all days after birth. The detection of AQP2 in early neonatal kidneys indicates that a lack of this protein is not responsible for the relatively weak urinary concentrating response to vasopressin seen in neonatal rats.
 ...
PMID:The AQP2 water channel: effect of vasopressin treatment, microtubule disruption, and distribution in neonatal rats. 753 96

The sites of water transport along the nephron are well characterized, but the molecular basis of renal water transport remains poorly understood. CHIP28 is a 28-kD integral protein which was proposed to mediate transmembrane water movement in red cells and kidney (Preston, G. M., T. P. Carroll, W. B. Guggino, and P. Agre. 1992. Science [Wash. DC]. 256:385-387). To determine whether CHIP28 could account for renal epithelial water transport, we used specific polyclonal antibodies to quantitate and localize CHIP28 at cellular and subcellular levels in rat kidney using light and electron microscopy. CHIP28 comprised 3.8% of isolated proximal tubule brush border protein. Except for the first few cells of the S1 segment, CHIP28 was immunolocalized throughout the convoluted and straight proximal tubules where it was observed in the microvilli of the apical brush border and in basolateral membranes. Very little CHIP28 was detected in endocytic vesicles or other intracellular structures in proximal tubules. Uninterrupted, heavy immunostaining of CHIP28 was also observed over both apical and basolateral membranes of descending thin limbs, including both short and long loops of Henle. These nephron sites have constitutively high osmotic water permeabilities. CHIP28 was not detected in ascending thin limbs, thick ascending limbs, or distal tubules, which are highly impermeable to water. Moreover, CHIP28 was not detected in collecting duct epithelia, where water permeability is regulated by antidiuretic hormone. These determinations of abundance and structural organization provide evidence that the CHIP28 water channel is the predominant pathway for constitutive transepithelial water transport in the proximal tubule and descending limb of Henle's loop.
 ...
PMID:CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. 767 19

Despite several decades of research interest and productivity, many aspects of hyponatremia and hypo-osmolar disorders remain incompletely understood. Among these aspects are questions relating to the morbidity and mortality actually attributable to hyponatremia, possible hormonal and gender-associated risk factors underlying susceptibility to neurologic complications from hyponatremic encephalopathy, the stimuli to arginine vasopressin secretion in some atypical subsets of patients with the syndrome of inappropriate antidiuretic hormone secretion and other hyponatremic disorders, the contributions of natriuresis and natriuretic peptides to hyponatremic states, the pathologic determinants of brain demyelination that sometimes follow rapid correction of hyponatremia, and appropriate treatment guidelines for patients with acute and chronic hyponatremia. The recent literature confirms that acceptable answers to these questions and others are still not available, and a better understanding of basic issues regarding the pathophysiology of hyponatremia is needed. Several recent advances stand out as being likely to enhance our future understanding of hyponatremia and hypo-osmolar states. First are studies of cellular mechanisms of volume regulation in kidney and brain tissue in response to changes in osmolality. Many, though clearly not all, clinical observations can be better understood by considering them in the conceptual framework provided by knowledge of cell and body fluid compartment volume regulation. Second is the elucidation of several important protein structures via complementary DNA cloning, including the arginine vasopressin V1 and V2 receptors, several organic osmolyte transporters, and the CHIP28 water channel. Future application of these new tools to carefully designed and executed physiologic studies will likely add considerable new knowledge to our understanding of hyponatremia. Third is the development and increasing application of nuclear magnetic resonance spectroscopy and imaging methods that will allow more detailed analyses of acute changes in brain metabolism during hyponatremia and following correction. Finally, the recent development of nonpeptide antagonists to arginine vasopressin V1 and V2 receptors should enable clinical studies to assess more accurately the contribution of arginine vasopressin-induced antidiuresis to hyponatremia and more importantly holds the promise of more effective therapies for hyponatremic patients.
 ...
PMID:Hyponatremia: epidemiology, pathophysiology, and therapy. 785 27

Concentrating urine is mandatory for most mammals to prevent water loss from the body. Concentrated urine is produced in response to vasopressin by the transepithelial recovery of water from the lumen of the kidney collecting tubule through highly water-permeable membranes. In this nephron segment, vasopressin regulates water permeability by endo- and exocytosis of water channels from or to the apical membrane. CHIP28 is a water channel in red blood cells and the kidney proximal tubule, but it is not expressed in the collecting tubule. Here we report the cloning of the complementary DNA for WCH-CD, a water channel of the apical membrane of the kidney collecting tubule. WCH-CD is 42% identical in amino-acid sequence to CHIP28. WCH-CD transcripts are detected only in the collecting tubule of the kidney. Immunohistochemically, WCH-CD is localized to the apical region of the kidney collecting tubule cells. Expression of WCH-CD in Xenopus oocytes markedly increases osmotic water permeability. The functional expression and the limited localization of WCH-CD to the apical region of the kidney collecting tubule suggest that WCH-CD is the vasopressin-regulated water channel.
 ...
PMID:Cloning and expression of apical membrane water channel of rat kidney collecting tubule. 842 10

Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel in the kidney collecting duct. AQP-2 is selectively permeable to water molecule and is translocated between the apical membrane and subapical endosomes in response to vasopressin. To investigate the localization and structure of the aqueous pathway of the AQP-2 water channel, a series of site-directed mutants was constructed and functionally analyzed. Insertion of N-glycosylation reporter sequence into each hydrophilic loop (HL) indicated that AQP-2 has a six-membrane spanning topology and that insertional mutations in HL-2 or HL-5 do not alter water channel function. Mercury-sensitive site of AQP-2 is located near the second asparagine-proline-alanine (NPA) domain at cysteine 181, but not near the first NPA domain. Replacement of HL-3 or HL-4 with the corresponding part of Escherichia coli glycerol facilitator abolished water channel function without changing plasma membrane expression of the channel protein. Introduction of cysteine residues in His-122, Asn-123, Gly-154, Asp-155, or Asn-156 induced partial mercury sensitivity, and point mutations in asparagine 123 significantly altered water permeability. Our results implicate that the structure of AQP-2 is different from models previously proposed for AQP-1 and that HL-3 and HL-4 are closely located to the aqueous pathway.
 ...
PMID:Structure of aquaporin-2 vasopressin water channel. 861 98

This review summarizes recent progress in water-transporting mechanisms across cell membranes. Modern biophysical concepts of water transport and new measurement strategies are evaluated. A family of water-transporting proteins (water channels, aquaporins) has been identified, consisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and cellular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surrounding a central aqueous pathway and functions independently as a water-selective channel. Only mutations in the vasopressin-sensitive water channel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of other water channels remains unproven. One mercurial-insensitive water channel has been identified, which has the unique feature of multiple overlapping transcriptional units. Systems for expression of water channel proteins are described, including Xenopus oocytes, mammalian and insect cells, and bacteria. Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.
 ...
PMID:Water transport across mammalian cell membranes. 877 26

Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects (n = 5), uremic patients treated by hemodialysis (n = 7) or PD (n = 4), and nonuremic patients (n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35-50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever their origin, eNOS (135 kDa) is upregulated in the three patients with ascites and/or peritonitis (1 PD and 2 nonuremic patients). AQP-2, regulated by vasopressin, is not expressed at the protein level in human peritoneum. This study 1) supports AQP-1 as the molecular counterpart of the ultrasmall pore in the human peritoneum and 2) demonstrates that AQP-1 and eNOS are regulated independently of each other in clinical conditions characterized by peritoneal inflammation.
 ...
PMID:Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum. 968 19

Recently, considerable evidence has been accumulated to support the novel view that water homeostasis in the inner ear is regulated via the vasopressin-aquaporin 2 (VP-AQP2) system in the same fashion as in the kidney. Indeed, multiple subtypes of AQPs including AQP-2 are reported to be expressed in the cochlea. However, the mechanism that underlies VP-AQP-2 mediated water homeostasis remains to be elucidated. In the present study, the localizations of AQP-1, -2, -3, -4, -5, -7, -8, -9, and vasopressin type 2 receptor (V2-R) in the stria vascularis (SV) were molecular biologically and immunohistochemically examined to evaluate the role of the AQP water channel system in water homeostasis of the SV. A RT-PCR study revealed that AQPs and V2-R mRNA are expressed in the cochlea. As for their immunohistochemical localization, the AQP-2 protein is expressed on the basal side of the basal cells of the SV, and proteins of AQP-3 and V2-R are expressed on the apical side of the basal cells. AQP-7 and -9 proteins are expressed on the apical side of marginal cells. AQP-4, -5, and -8 protein expressions could not be detected in the lateral wall of the cochlea. From the present results, water flux in the SV is thought to be regulated at the level of the basal cells by vasopressin. Furthermore, such a distribution of AQP-2, -3, and V2-R suggests that VP-AQP-2 mediated water transport might work actively in the basal cells from perilymph towards endolymph containing AQP-1, -7 and -9.
 ...
PMID:Expression of aquaporins and vasopressin type 2 receptor in the stria vascularis of the cochlea. 1979 72


1